In vivo single-cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection.
In vivo single-cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection.
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体内单细胞转录组学研究揭示肺炎克雷伯菌使肺巨噬细胞发生偏向性改变以促进感染 。
DOI：
10.15252/emmm.202216888
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发表时间：
2022-12-07
影响因子：
11.1
通讯作者：
Bengoechea, Jose A.
中科院分区：
文献类型：
--
作者：
Dumigan, Amy;Cappa, Oisin;Morris, Brenda;Pessoa, Joana Sa;Calderon-Gonzalez, Ricardo;Mills, Grant;Lancaster, Rebecca;Simpson, David;Kissenpfennig, Adrien;Bengoechea, Jose A.
抗生素耐药细菌对抗宿主防御的策略尚不清楚。在这里，我们阐明了一种新的宿主-病原体相互作用，导致人类病原体肺炎克雷伯菌的肺巨噬细胞偏斜极化。我们确定间质巨噬细胞（IMs）是与克雷伯氏菌相关的肺巨噬细胞的主要群体。单细胞转录组学和细胞轨迹分析显示，I型IFN和IL10信号传导和巨噬细胞极化是感染IMs的特征，而Toll样受体（TLR）和Nod样受体信号传导是感染肺泡巨噬细胞的特征。克雷伯菌诱导的巨噬细胞极化是一种单一的M2型，我们称之为M（Kp）。为了重新连接巨噬细胞，克雷伯菌劫持了TLR - I型IFN - IL10 - STAT6轴。缺乏STAT6限制了克雷伯菌在细胞内的存活，并促进了病原体在体内的清除。糖酵解的特点是M（Kp）代谢，抑制糖酵解导致细胞内克雷伯菌的清除。胶囊多糖支配M（Kp）。克雷伯氏菌还以I型IFN‐IL10‐STAT6依赖性的方式使人巨噬细胞向M（Kp）极化。克雷伯氏菌诱导M（Kp）代表了一种克服宿主限制的新策略，并将STAT6确定为增强克雷伯氏菌防御的靶标。肺炎克雷伯菌是抗生素耐药感染对公共卫生威胁的例证。克雷伯氏菌是如何适应免疫系统，在呼吸道等组织中繁衍生息的，目前还不太清楚。在这里，克雷伯氏菌使肺巨噬细胞扭曲到一个新的状态来克服宿主的限制。
The strategies deployed by antibiotic‐resistant bacteria to counteract host defences are poorly understood. Here, we elucidate a novel host–pathogen interaction resulting in skewing lung macrophage polarisation by the human pathogen Klebsiella pneumoniae. We identify interstitial macrophages (IMs) as the main population of lung macrophages associated with Klebsiella. Single‐cell transcriptomics and trajectory analysis of cells reveal type I IFN and IL10 signalling, and macrophage polarisation are characteristic of infected IMs, whereas Toll‐like receptor (TLR) and Nod‐like receptor signalling are features of infected alveolar macrophages. Klebsiella‐induced macrophage polarisation is a singular M2‐type we termed M(Kp). To rewire macrophages, Klebsiella hijacks a TLR‐type I IFN‐IL10‐STAT6 axis. Absence of STAT6 limits Klebsiella intracellular survival and facilitates the clearance of the pathogen in vivo. Glycolysis characterises M(Kp) metabolism, and inhibition of glycolysis results in clearance of intracellular Klebsiella. Capsule polysaccharide governs M(Kp). Klebsiella also skews human macrophage polarisation towards M(Kp) in a type I IFN‐IL10‐STAT6‐dependent manner. Klebsiella induction of M(Kp) represents a novel strategy to overcome host restriction, and identifies STAT6 as target to boost defences against Klebsiella. Klebsiella pneumoniae exemplifies the threat of antibiotic resistant infections to public health. How Klebsiella adapts to the immune system to flourish in tissues such as the airways remains poorly understood. Here, Klebsiella skews lung macrophages to a new state to overcome host restriction.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
3.1
作者：
BrougHolub, E;Toews, GB;Standiford, TJ
通讯作者：
Standiford, TJ
影响因子：
30.5
作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
通讯作者：
Wack, Andreas
影响因子：
3.1
作者：
Bartholomew, Toby L.;Kidd, Timothy J.;Bengoechea, Jose A.
通讯作者：
Bengoechea, Jose A.
影响因子：
8
作者：
Arafa EI;Shenoy AT;Barker KA;Etesami NS;Martin IM;Lyon De Ana C;Na E;Odom CV;Goltry WN;Korkmaz FT;Wooten AK;Belkina AC;Guillon A;Forsberg EC;Jones MR;Quinton LJ;Mizgerd JP
通讯作者：
Mizgerd JP